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Vegetation greening has long been acknowledged, but recent studies have pointed out that vegetation greening is possibly stalled or even reversed. However, detailed analyses about greening reversal or increased browning of vegetation remain scarce. In this study, we utilized the normalized difference vegetation index (NDVI) as an indicator of vegetation to investigate the trends of vegetation greening and browning (monotonic, interruption, and reversal) through the breaks for the additive season and trend (BFAST) method across China’s drylands from 1982 to 2022. It also reveals the impacts of ecological restoration programs (ERPs) and climate change on these vegetation trends. We find that the vegetation displays an obvious pattern of east-greening and west-browning in China’s drylands. Greening trends mainly exhibits monotonic greening (29.8 %) and greening with setback (36.8 %), whereas browning shows a greening to browning reversal (19.2 %). The increase rate of greening to browning reversal is 0.0342/yr, which is apparently greater than that of greening with setback, 0.0078/yr. This research highlights that, under the background of widespread vegetation greening, vegetation browning is progressively increasing due to the effects of climate change. Furthermore, the ERPs have significantly increased vegetation coverage, with the increase rate in 2000–2022 being twice as much as that of 1982–1999 in revegetation regions. Vegetation browning in southwestern Qingzang Plateau is primarily driven by adverse climatic factors and anthropogenic disturbances, which offset the efforts of ERPs.

Abstract Tumor cells can survive when detached from the extracellular matrix (ECM) or lose cell–cell connections, a phenomenon known as anoikis-resistance (AR). AR is closely associated with tumor cell metastasis and recurrence, enabling tumor cells to disseminate, migrate, and invade after detachment. To address this issue, a novel intervention method combining intraoperative hemostasis with multifunctional nanozyme driven-enhanced chemodynamic therapy (ECDT) has been proposed, which holds the potential to weaken the AR capability of tumor cells and suppress tumor recurrence. Here, a nanocomposite containing a dendritic mesoporous nanoframework with Cu2+ was developed using an anion-assisted approach after surface PEG grafting and glucose oxidase (GOx) anchoring (DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG was further encapsulated in a thermal-sensitive hydrogel (H@DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG utilizes its high peroxidase (POD) activity to elevate intracellular ROS levels, thereby weakening the AR capability of bladder cancer cells. Additionally, through its excellent catalase (CAT) activity, DMSN-Cu@GOx/PEG converts the high level of hydrogen peroxide (H2O2) catalyzed by intracellular GOx into oxygen (O2), effectively alleviating tumor hypoxia, downregulating hypoxia-inducible factor-1α (HIF-1α) expression, inhibiting epithelial-mesenchymal transition (EMT) processes, and ultimately suppressing the migration and invasion of bladder cancer cells. Interestingly, in vivo results showed that the thermosensitive hydrogel H@DMSN-Cu@GOx/PEG could rapidly gel at body temperature, forming a gel film on wounds to eliminate residual tumor tissue after tumor resection surgery. Importantly, H@DMSN-Cu@GOx/PEG exhibited excellent hemostatic capabilities, effectively enhancing tissue coagulation during post-tumor resection surgery and mitigating the risk of cancer cell dissemination and recurrence due to surgical bleeding. Such hydrogels undoubtedly possess strong surgical application. Our developed novel nanosystem and hydrogel can inhibit the AR capability of tumor cells and prevent recurrence post-surgery. This study represents the first report of using dendritic mesoporous silica-based nanoreactors for inhibiting the AR capability of bladder cancer cells and suppressing tumor recurrence post-surgery, providing a new avenue for developing strategies to impede tumor recurrence after surgery. Graphical Abstract

Abstract The world’s oceans are under threat from the prevalence of heatwaves caused by climate change. Despite this, there is a lack of understanding regarding their impact on seawater oxygen levels - a crucial element in sustaining biological survival. Here, we find that heatwaves can trigger low-oxygen extreme events, thereby amplifying the signal of deoxygenation. By utilizing in situ observations and state-of-the-art climate model simulations, we provide a global assessment of the relationship between the two types of extreme events in the surface ocean (0–10 m). Our results show compelling evidence of a remarkable surge in the co-occurrence of marine heatwaves and low-oxygen extreme events. Hotspots of these concurrent stressors are identified in the study, indicating that this intensification is more pronounced in high-biomass regions than in those with relatively low biomass. The rise in the compound events is primarily attributable to long-term warming primarily induced by anthropogenic forcing, in tandem with natural internal variability modulating their spatial distribution. Our findings suggest the ocean is losing its breath under the influence of heatwaves, potentially experiencing more severe damage than previously anticipated.

Abstract Purpose Osteosarcoma is a primary bone tumor lacking optimal clinical treatment options. Tumor-associated macrophages in the tumor microenvironment are closely associated with tumor development and metastasis. Studies have identified the macrophage receptor with collagenous structure (MARCO) as a specific receptor expressed in macrophages. This study aimed to investigate whether anti-MARCO mAb treatment can induce macrophage polarization in the tumor microenvironment and elicit anti-tumor effects. Methods THP-1 cells were treated with 20 ng/mL phorbol 12-myristate 13-acetate and 80 ng/mL interleukin-4 for 48 h to induce macrophage polarization to alternatively activated macrophages (M2). Enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, flow cytometry, and bioinformatic analyses were performed to evaluate macrophage polarization. The co-culture groups included a blank group, an M2 macrophage and U2OS co-culture group, and an anti-MARCO mAb-treated M2 macrophage group. Cell viability assays, cell scratch tests, apoptosis, and cell cycle analyses were performed to determine the effects of anti-MARCO mAb-treated macrophages on osteosarcoma cells. Results It was demonstrated that anti-MARCO mAb can drive macrophages toward classically activated macrophage (M1) polarization. Anti-MARCO mAb promoted the secretion of pro-inflammatory factors by macrophages, including tumor necrosis factor-alpha (TNF-α), interleukin-1beta, interleukin-6 and interleukin-23. Studies on in vitro co-culture models have revealed that macrophages treated with anti-MARCO mAb can suppress the growth and migration of osteosarcoma cells, induce cell apoptosis, and inhibit cell cycle progression of osteosarcoma cells through M1 polarization of macrophages in vitro. Conclusion Anti-MARCO mAb treatment exerts anti-osteosarcoma effects by affecting macrophage polarization toward M1 macrophages, offering a potential new therapeutic approach for treating osteosarcoma.

Abstract Background The interplay between atrial fibrillation (AF) and obesity on mortality in critically ill patients warrants detailed exploration, given their individual impacts on patient prognosis. This study aimed to assess the associations between AF, obesity, and 1-year mortality in a critically ill population. Methods Utilizing data from the Medical Information Mart for Intensive Care (MIMIC)-IV database, we conducted a retrospective analysis of adult patients admitted to the intensive care unit. The primary endpoint was 1-year mortality, analyzed through Cox regression with hazard ratio (HR) and Kaplan-Meier survival methods. Results The study included 25,654 patients (median age 67.0 years, 40.6% female), with 39.0% having AF and 36.1% being obese. Multivariate COX regression analysis revealed that AF was associated with a 14.7% increase in the risk of 1-year mortality (p

Highlights Electrodeposited amorphous IrO x thin electrodes are first developed for proton exchange membrane electrolyzer cells. An ultralow loading of 0.075 mg cm−2 archives superior performance to catalyst-coated membrane (2 mg cm−2). > 96% of catalyst savings and > 42-fold higher catalyst utilization are demonstrated.

Abstract Background The relationship between triglyceride glucose-body mass index (TyG-BMI) index and mortality in elderly patients with diabetes mellitus (DM) are still unclear. This study aimed to investigate the association between TyG-BMI with all-cause and cardiovascular mortality among elderly DM patients in the United States (US). Methods Patients aged over 60 years with DM from the National Health and Nutrition Examination Survey (2007–2016) were included in this study. The study endpoints were all-cause and cardiovascular mortality and the morality data were extracted from the National Death Index (NDI) which records up to December 31, 2019. Multivariate Cox proportional hazards regression model was used to explore the association between TyG-BMI index with mortality. Restricted cubic spline was used to model nonlinear relationships. Results A total of 1363 elderly diabetic patients were included, and were categorized into four quartiles. The mean age was 70.0 ± 6.8 years, and 48.6% of them were female. Overall, there were 429 all-cause deaths and 123 cardiovascular deaths were recorded during a median follow-up of 77.3 months. Multivariate Cox regression analyses indicated that compared to the 1st quartile (used as the reference), the 3rd quartile demonstrated a significant association with all-cause mortality (model 2: HR = 0.64, 95% CI 0.46–0.89, P = 0.009; model 3: HR = 0.65, 95% CI 0.43–0.96, P = 0.030). Additionally, the 4th quartile was significantly associated with cardiovascular mortality (model 2: HR = 1.83, 95% CI 1.01–3.30, P = 0.047; model 3: HR = 2.45, 95% CI 1.07–5.57, P = 0.033). The restricted cubic spline revealed a U-shaped association between TyG-BMI index with all-cause mortality and a linear association with cardiovascular mortality, after adjustment for possible confounding factors. Conclusions A U-shaped association was observed between the TyG-BMI index with all-cause mortality and a linear association was observed between the TyG-BMI index with cardiovascular mortality in elderly patients with DM in the US population.

Abstract Intestinal stem cells (ISCs) play a crucial role in the continuous self-renewal and recovery of the intestinal epithelium. In previous studies, we have revealed that the specific absence of Claudin-7 (Cldn-7) in intestinal epithelial cells (IECs) can lead to the development of spontaneous colitis. However, the mechanisms by which Cldn-7 maintains homeostasis in the colonic epithelium remain unclear. Therefore, in the present study, we used IEC- and ISC-specific Cldn-7 knockout mice to investigate the regulatory effects of Cldn-7 on colonic Lgr5+ stem cells in the mediation of colonic epithelial injury and repair under physiological and inflammatory conditions. Notably, our findings reveal that Cldn-7 deletion disrupts the self-renewal and differentiation of colonic stem cells alongside the formation of colonic organoids in vitro. Additionally, these Cldn-7 knockout models exhibited heightened susceptibility to experimental colitis, limited epithelial repair and regeneration, and increased differentiation toward the secretory lineage. Mechanistically, we also established that Cldn-7 facilitates the proliferation, differentiation, and organoid formation of Lgr5+ stem cells through the maintenance of Wnt and Notch signalling pathways in the colonic epithelium. Overall, our study provides new insights into the maintenance of ISC function and colonic epithelial homoeostasis.

Abstract Background Previous studies have unequivocally demonstrated that the vitamin D (VD) metabolism pathway significantly influences prognosis and sensitivity to hormone therapy in prostate cancer (PCa). However, the precise underlying mechanism remains unclear. Methods We performed molecular profiling of 1045 PCa patients, leveraging genes linked to VD synthesis and VD receptors. We then identified highly variable gene modules with substantial associations with patient stratification. Subsequently, we intersected these modules with differentially expressed genes between PCa and adjacent paracancerous tissues. Following a meticulous process involving single-factor regression and LASSO regression to eliminate extraneous variables and construct a prognostic model. Within the high-risk subgroup defined by the calculated risk score, we analyzed their differences in cell infiltration, immune status, mutation landscape, and drug sensitivity. Finally, we selected Apolipoprotein E (APOE), which featured prominently in this model for further experimental exploration to evaluate its potential as a therapeutic target. Results The prognostic model established in this study had commendable predictive efficacy. We observed diminished infiltration of various T-cell subtypes and reduced expression of co-stimulatory signals from antigen-presenting cells. Mutation analysis revealed that the high-risk cohort harbored a higher frequency of mutations in the TP53 and FOXA genes. Notably, drug sensitivity analysis suggested the heightened responsiveness of high-risk patients to molecular inhibitors targeting the Bcl-2 and MAPK pathways. Finally, our investigation also confirmed that APOE upregulates the proliferative and invasive capacity of PCa cells and concurrently enhances resistance to androgen receptor antagonist therapy. Conclusion This comprehensive study elucidated the potential mechanisms through which this metabolic pathway orchestrates the biological behavior of PCa and findings hold promise in advancing the development of combination therapies in PCa.

Abstract Aims We aimed to evaluate the effects of radiofrequency catheter ablation (RFCA) and the factors influencing mortality after RFCA in patients with pulmonary hypertension (PH) and atrial flutter (AFL). Methods and results Fifty‐eight consecutive PH patients with AFL who underwent an electrophysiological study and RFCA between April 2013 and August 2021 were selected for this study. In the study population, pulmonary arterial hypertension associated with congenital heart disease (PAH‐CHD) was the most common type of PH (n = 34, 59%), followed by idiopathic pulmonary arterial hypertension (IPAH) (n = 19, 33%). Typical atrial flutter was the most common type of atrial flutter (n = 50, 86.2%). Sinus rhythm was restored in 53 (91.4%) patients during RFCA. After a mean follow‐up of 33.8 months, AFL recurred in a total of 22 patients. Nine of them underwent repeat RFCA, and the site of the repeat ablation was not exactly the same as the first. At a median follow‐up of 34.6 months after the last ablation, none of the patients who underwent repeat RFCA experienced AFL recurrence, and all of these patients survived. There were no procedure‐related complications during hospitalization or follow‐up. Univariate Cox regression analysis suggested that AFL recurrence after the last ablation was not associated with all‐cause mortality. NT‐proBNP (HR: 1.00024, 95% CI: 1.00008–1.00041, P = 0.004), pulmonary artery systolic pressure (PASP) (HR: 1.048, 95% CI: 1.020–1.076, P = 0.001), and IPAH (vs. PAH‐CHD, HR: 7.720, 95% CI: 1.437–41.483, P = 0.017) were independent predictors of all‐cause mortality in PH patients with AFL after RFCA. Receiver operating characteristic (ROC) curve analysis revealed that the area under the curve (AUC) of PASP for predicting all‐cause mortality was 0.708. There was no significant difference in the Kaplan–Meier curves for all‐cause mortality between patients with AFL recurrence after the last ablation and those without recurrence (P = 0.851). Patients with higher PASP (≥110 mmHg) and IPAH showed the lower survival rate in Kaplan–Meier curves. Conclusion Repeat ablation was safe and feasible in patients with recurrent AFL and can maintain sinus rhythm. AFL recurrence was not associated with all‐cause mortality, and patients with high PASP or IPAH were at higher risk for adverse outcomes.

Traditionally, virtual inertia is used as the control strategy for wind turbines when participating in frequency regulation. However, it has inherent defects in measurement error amplification due to the frequency differential. Also, when control delay of wind turbines is taken into consideration, virtual inertia is essentially a fast power response, just the same as droop control. Hence, considering the adaptability of droop control, it is valuable to explore a novel droop control method without virtual inertia, as the frequency response model of wind turbines. For this reason, a multi-segment droop control strategy is proposed to provide a reliable frequency regulation model for wind turbines that can be broadly applied to other inverter-based power sources. Firstly, based on the extended system frequency response model, a differential equation including piecewise time-varying coefficients is established, and the analytical expression of the frequency response is obtained using the impulse function balancing principle and the integration by parts algorithm. Subsequently, based on analytical expression, the performance of the presented strategy is theoretically analyzed via comparison with virtual inertia control, and the conclusion that the presented multi-segment droop control has better frequency regulation performance can be got. Furthermore, to achieve optimal frequency regulation performance, a Lagrangian function is established to determine the optimal parameters of the proposed control strategy. Finally, the performance of the proposed strategy was verified in a two-area system model constructed on MATLAB/Simulink. Results show that the proposed multi-segment droop control has better frequency regulation performance.

Abstract Background Laparoscopic surgery has been endorsed by clinical guidelines for colon cancer, but not for rectal cancer on account of unapproved oncologic equivalence with open surgery. Aims We started this largest‐to‐date meta‐analysis to comprehensively evaluate the safety and efficacy of laparoscopy in the treatment of rectal cancer compared with open surgery. Materials & Methods Both randomized and nonrandomized controlled trials comparing laparoscopic proctectomy and open surgery between January 1990 and March 2020 were searched in PubMed, Cochrane Library and Embase Databases (PROSPERO registration number CRD42020211718). The data of intraoperative, pathological, postoperative and survival outcomes were compared between two groups. Results Twenty RCTs and 93 NRCTs including 216,615 patients fulfilled the inclusion criteria, with 48,888 patients received laparoscopic surgery and 167,727 patients underwent open surgery. Compared with open surgery, laparoscopic surgery group showed faster recovery, less complications and decreased mortality within 30 days. The positive rate of circumferential margin (RR = 0.79, 95% CI: 0.72 to 0.85, p

Summary: Sunitinib, a primary treatment for clear cell renal cell carcinoma (ccRCC), frequently encounters the challenge of resistance development. Metabolic reprogramming, a characteristic change in ccRCC, is likely linked to this resistance. Our research revealed a notable decrease in the expression of the key metabolic gene ABAT in ccRCC, which contributed to diminished sensitivity to sunitinib. Downregulation of ABAT led to an increase in the intracellular level of gamma-aminobutyric acid (GABA), triggering abnormal activation of the G-protein-coupled receptor GABA-B. This activation resulted in increased transactivation of the tyrosine kinase receptors SYK and LYN, thereby reducing the antitumor and antiangiogenic properties of sunitinib. However, the application of SYK and LYN inhibitors successfully inhibited this effect. The transactivation of SYK and LYN caused resistance to the antiangiogenic effects of sunitinib through the upregulation of PGF protein levels. Furthermore, the combined application of an LYN inhibitor with sunitinib has been shown to enhance therapeutic efficacy.

Epidemiological evidence indicates an association between exposure to toxic metals and the occurrence of cardiometabolic diseases (CMDs). However, the impact of exposure to harmful metallic elements, such as lead (Pb), cadmium (Cd), and mercury (Hg), on mortality in individuals with cardiometabolic multimorbidity (CMM) remains uncertain. Therefore, in this study, we analyzed data from 4139 adults diagnosed with CMM from the National Health and Nutrition Examination Survey 1999–2016. CMM was defined as the presence of at least two CMDs (hypertension, diabetes, stroke, and coronary artery disease). Over an average follow-up period of 9.0 years, 1379 deaths from all causes, 515 deaths related to cardiovascular disease (CVD), and 215 deaths attributable to cancer were recorded. After adjusting for potential covariates, serum Pb concentrations were not associated with all-cause, CVD, or cancer mortality. Participants exposed to Cd had an elevated risk of all-cause mortality (hazard ratio [HR], 1.23; 95 % CI, 1.16–1.30), CVD-related mortality (HR, 1.23; 95 % CI, 1.12–1.35), and cancer-related mortality (HR, 1.29; 95 % CI, 1.13–1.47). Participants with serum Hg levels in the highest quantile had lower risks of all-cause (HR, 0.64; 95 % CI, 0.52–0.80) and CVD-related (HR, 0.62; 95 % CI, 0.44–0.88) mortality than did those in the lowest quantile. Stratified analyses revealed significant interactions between serum Cd concentrations and age for CVD-related mortality (P for interaction =0.011), indicating that CMM participants aged < 60 years who were exposed to Cd were at a greater risk of CVD-related mortality. A nonlinear relationship was observed between serum Cd concentrations and all-cause (P for nonlinear relationship = 0.012) and CVD-related (P for nonlinear relationship < 0.001) mortality. Minimizing Cd exposure in patients with CMM may help prevent premature death.

Abstract Membrane consisting of ordered sub-nanochannels has been pursued in ion separation technology to achieve applications including desalination, environment management, and energy conversion. However, high-precision ion separation has not yet been achieved owing to the lack of deep understanding of ion transport mechanism in confined environments. Biological ion channels can conduct ions with ultrahigh permeability and selectivity, which is inseparable from the important role of channel size and “ion-channel” interaction. Here, inspired by the biological systems, we report the high-precision separation of monovalent and divalent cations in functionalized metal-organic framework (MOF) membranes (UiO-66-(X)2, X = NH2, SH, OH and OCH3). We find that the functional group (X) and size of the MOF sub-nanochannel synergistically regulate the ion binding affinity and dehydration process, which is the key in enlarging the transport activation energy difference between target and interference ions to improve the separation performance. The K+/Mg2+ selectivity of the UiO-66-(OCH3)2 membrane reaches as high as 1567.8. This work provides a gateway to the understanding of ion transport mechanism and development of high-precision ion separation membranes.

Abstract Background The Stress hyperglycemia ratio (SHR) is a novel marker reflecting the true acute hyperglycemia status and is associated with clinical adverse events. The relationship between SHR and mortality in patients with diabetes or prediabetes is still unclear. This study aimed to investigate the predictive value of the SHR for all-cause and cardiovascular mortality in patients with diabetes or prediabetes. Methods This study included 11,160 patients diagnosed with diabetes or prediabetes from the National Health and Nutrition Examination Survey (2005–2018). The study endpoints were all-cause and cardiovascular mortality, and morality data were extracted from the National Death Index (NDI) up to December 31, 2019. Patients were divided into SHR quartiles. Cox proportion hazards regression was applied to determine the prognostic value of SHR. Model 1 was not adjusted for any covariates. Model 2 was adjusted for age, sex, and race. Model 3 was adjusted for age, sex, race, BMI, smoking status, alcohol use, hypertension, CHD, CKD, anemia, and TG. Results During a mean follow-up of 84.9 months, a total of 1538 all-cause deaths and 410 cardiovascular deaths were recorded. Kaplan-Meier survival analysis showed the lowest all-cause mortality incidence was in quartile 3 (P

Abstract Objectives To develop a deep learning (DL) model for differentiating between osteolytic osteosarcoma (OS) and giant cell tumor (GCT) on radiographs. Methods Patients with osteolytic OS and GCT proven by postoperative pathology were retrospectively recruited from four centers (center A, training and internal testing; centers B, C, and D, external testing). Sixteen radiologists with different experiences in musculoskeletal imaging diagnosis were divided into three groups and participated with or without the DL model’s assistance. DL model was generated using EfficientNet-B6 architecture, and the clinical model was trained using clinical variables. The performance of various models was compared using McNemar’s test. Results Three hundred thirty-three patients were included (mean age, 27 years ± 12 [SD]; 186 men). Compared to the clinical model, the DL model achieved a higher area under the curve (AUC) in both the internal (0.97 vs. 0.77, p = 0.008) and external test set (0.97 vs. 0.64, p

Abstract Background Although the disturbance of circadian rhythms represents a significant clinical feature of major depressive disorder (MDD), the relationship between biological rhythm disturbances and the severity of suicidal ideation in individuals with MDD remains unclear. We aimed to explore the characteristics of different biological rhythm dimensions in MDD and their association with the severity of depressive symptoms and suicidal ideation. Methods A total of 50 MDD patients and 50 healthy controls were recruited and their general information was collected. The severity of depressive symptoms was assessed with the 17-item Hamilton Depression Rating Scale (HDRS17). The intensity of suicidal ideation was evaluated with the Beck Scale for Suicide Ideation (BSS). The Chinese version of the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) scale was utilized to assess the participants’ biological rhythm dysregulation. Multiple logistic regression analysis was conducted to explore the relationship between biological rhythm and the risk of MDD. Multiple linear regression analysis was performed in the MDD group to investigate the relationship between different biological rhythm dimensions and suicide ideation. Results Significant differences were observed between the MDD group and the control group in total BRIAN score (Z=-5.41, P

Abstract Anomaly detection is a highly important task in the field of data analysis. Traditional anomaly detection approaches often strongly depend on data size, structure and features, while introducing the idea of ensemble into anomaly detection can greatly improve the generalization ability. Ensemble-based anomaly detection methods still face some challenges, however, such as data imbalance, time and space demand and the selection of base detectors. To this end, we propose a selective ensemble method for anomaly detection based on parallel learning (SEAD-PL). First, a differentiated stratified sampling method is designed to alleviate the problem of data imbalance. Then, a distributed parallel training frame is built to address the problem of excessive time and space consumption for base detector training. Finally, a clustering-based ensemble selection strategy is introduced to balance the accuracy and diversity of base detectors. Experiments are performed on six datasets, which demonstrate that the proposed method has obvious advantages over four selected methods.

Abstract Aim The commonly recommended endotracheal tube cuff pressure is 20–30 cmH2O. However, some patients require a cuff pressure of >30 cmH2O to prevent air leakage. The study aims to determine the risk factors that contribute to the endotracheal tube cuff pressure of >30 cmH2O to prevent air leakage. Design A multi‐centre prospective observational study. Methods Eligible patients undergoing mechanical ventilation in the intensive care unit of three hospitals between March 2020 and July 2022 were included. The endotracheal tube cuff pressure to prevent air leakage was determined using the minimal occlusive volume technique. The patient demographics and clinical information were collected. Results A total of 284 patients were included. Among these patients, 55 (19.37%) patients required a cuff pressure of >30 cmH2O to prevent air leakage. The multivariate logistic regression results revealed that the surgical operation (odds ratio [OR]: 8.485, 95% confidence interval [CI]: 1.066–67.525, p = 0.043) was inversely associated with the endotracheal tube cuff pressure of >30 cmH2O, while the oral intubation route (OR: 0.127, 95% CI: 0.022–0.750, p = 0.023) and cuff inner diameter minus tracheal area (OR: 0.949, 95% CI: 0.933–0.966, p 30 cmH2O. Therefore, a significant number of patients require an endotracheal tube cuff pressure of ＞30 cmH2O to prevent air leakage. Several factors, including the surgical operation, intubation route, and difference between the cuff inner diameter and tracheal area at the T3 vertebra, should be considered when determining the appropriate cuff pressure during mechanical ventilation.

BackgroundThe COVID-19 pandemic has presented unique challenges to individuals worldwide, with a significant focus on the impact on sleep. However, the precise mechanisms through which emotional and cognitive variables mediate this relationship remain unclear. To expand our comprehensive understanding of variables, the present study utilizes the Preventive Stress Management theory, to test the relationship between perceived social support and sleep quality, as well as the effect of perceived COVID-19 stress, hope, negative emotions and coping styles.MethodsData were collected in March 2022 from 1,034 college students in two universities located in Liaoning Province, China, using an online survey platform regarding perceived social support, perceived COVID-19 stress, sleep quality, hope, negative emotions and coping styles. The moderated mediation model were conducted using Process macro program (Model 6) and the syntax in SPSS.ResultsThe results revealed perceived COVID-19 stress and negative emotions sequentially mediated the negative relationship between perceived social support and sleep quality. Furthermore, hope and coping styles were found to moderate the sequential mediating effect.ConclusionThe present study sheds light on the pathways that affect sleep quality among college students during the COVID-19 pandemic. Findings highlight the protective roles played by positive social and personal resources, such as perceived social support, hope, and effective coping styles, against sleep problems. These insights have important implications for the development of targeted interventions to improve sleep outcomes during this challenging time.

Abstract Background The vein of Marshall (VOM) ethanol infusion is increasingly performed in combination with catheter ablation in atrial fibrillation (AF). The cannulation of the VOM can sometimes be challenging. This study aimed to evaluate the double-wire technique in cases of difficult cannulation of the VOM. Case presentation Patients with AF scheduled for combined catheter ablation and VOM ethanol infusion were consecutively enrolled. The procedure was performed via the femoral vein. If the regular cannulation technique with one angioplasty wire failed or took more than 20 min, the double-wire technique using a stabilizing wire and a cannulation wire was performed. The unique technique was used mainly in two scenarios, when the Eustachian ridge was too prominent as a barrier for catheter manipulation or when the VOM ostium was close to the coronary sinus ostium. Of 162 patients scheduled for VOM ethanol infusion, the double-wire technique was applied in 6 (3.7%) patients and led to a 100% successful cannulation rate of the VOM. Of the six patients, two had a prominent Eustachian ridge, and four had a VOM ostium close to the coronary sinus ostium. The mean cannulation time was 33.3 ± 7.3 min. The ethanol infusion was successfully performed in 5 patients. One patient had a collateral circulation in the distal VOM, and ethanol infusion was not performed. Conclusions The double-wire technique can facilitate VOM cannulation and ethanol infusion in challenging cases. Word count : 231.

Glioblastoma (GBM) is an immunologically cold tumor, but several immunotherapy-based strategies show promise, including the administration of ex vivo expanded and activated cytotoxic gamma delta T cells. Cytotoxicity is partially mediated through interactions with natural killer group 2D ligands (NKG2DL) on tumor cells. We sought to determine whether the addition of the blood–brain barrier penetrant PARP inhibitor niraparib to the standard of care DNA alkylator temozolomide (TMZ) could upregulate NKG2DL, thereby improving immune cell recognition. Changes in viability were consistent with prior publications as there was a growth inhibitory effect of the combination of TMZ and niraparib. However, decreases in viability did not always correlate with changes in NKG2DL mRNA. ULBP1/Mult-1 mRNA was increased with the combination therapy in comparison to either drug alone in two of the three cell types tested, even though viability was consistently decreased. mRNA expression correlated with protein levels and ULBP1/MULT-1 cell surface protein was significantly increased with TMZ and niraparib treatment in four of the five cell types tested. Gamma delta T cell-mediated cytotoxicity at a 10:1 effector-to-target ratio was significantly increased upon pretreatment of cells derived from a GBM PDX with TMZ and niraparib in comparison to the control or either drug alone. Together, these data demonstrate that the combination of PARP inhibition, DNA alkylation, and gamma delta T cell therapy has the potential for the treatment of GBM.

BackgroundPrevious studies have confirmed the separate effect of arterial stiffness and obesity on type 2 diabetes; however, the joint effect of arterial stiffness and obesity on diabetes onset remains unclear. ObjectiveThis study aimed to propose the concept of arterial stiffness obesity phenotype and explore the risk stratification capacity for diabetes. MethodsThis longitudinal cohort study used baseline data of 12,298 participants from Beijing Xiaotangshan Examination Center between 2008 and 2013 and then annually followed them until incident diabetes or 2019. BMI (waist circumference) and brachial-ankle pulse wave velocity were measured to define arterial stiffness abdominal obesity phenotype. The Cox proportional hazard model was used to estimate the hazard ratio (HR) and 95% CI. ResultsOf the 12,298 participants, the mean baseline age was 51.2 (SD 13.6) years, and 8448 (68.7%) were male. After a median follow-up of 5.0 (IQR 2.0-8.0) years, 1240 (10.1%) participants developed diabetes. Compared with the ideal vascular function and nonobese group, the highest risk of diabetes was observed in the elevated arterial stiffness and obese group (HR 1.94, 95% CI 1.60-2.35). Those with exclusive arterial stiffness or obesity exhibited a similar risk of diabetes, and the adjusted HRs were 1.63 (95% CI 1.37-1.94) and 1.64 (95% CI 1.32-2.04), respectively. Consistent results were observed in multiple sensitivity analyses, among subgroups of age and fasting glucose level, and alternatively using arterial stiffness abdominal obesity phenotype. ConclusionsThis study proposed the concept of arterial stiffness abdominal obesity phenotype, which could improve the risk stratification and management of diabetes. The clinical significance of arterial stiffness abdominal obesity phenotype needs further validation for other cardiometabolic disorders.

Abstract Background We aimed to develop machine learning models for prediction of molecular subgroups (low-risk group and intermediate/high-risk group) and molecular marker (KIAA1549-BRAF fusion) of pediatric low-grade gliomas (PLGGs) based on radiomic features extracted from multiparametric MRI. Methods 61 patients with PLGGs were included in this retrospective study, which were divided into a training set and an internal validation set at a ratio of 2:1 based on the molecular subgroups or the molecular marker. The patients were classified into low-risk and intermediate/high-risk groups, BRAF fusion positive and negative groups, respectively. We extracted 5929 radiomic features from multiparametric MRI. Thereafter, we removed redundant features, trained random forest models on the training set for predicting the molecular subgroups or the molecular marker, and validated their performance on the internal validation set. The performance of the prediction model was verified by 3-fold cross-validation. Results We constructed the classification model differentiating low-risk PLGGs from intermediate/high-risk PLGGs using 4 relevant features, with an AUC of 0.833 and an accuracy of 76.2% in the internal validation set. In the prediction model for predicting KIAA1549-BRAF fusion using 4 relevant features, an AUC of 0.818 and an accuracy of 81.0% were achieved in the internal validation set. Conclusions The current study demonstrates that MRI radiomics is able to predict molecular subgroups of PLGGs and KIAA1549-BRAF fusion with satisfying sensitivity. Trial registration This study was retrospectively registered at clinicaltrials.gov (NCT04217018).

90Rb is a high-yield short-lived fission product, a highly sensitive detector for low fission burnup, and its half-life is an important nuclear parameter. At present, the ENSDF (Evaluated Nuclear Structure Data File) evaluated value for the half-life of 90Rb is (158±5) s (±3.2%). Due to the low energy resolution of early detectors such as Geiger counter, proportional counter and Ge(Li) detector and significant interference of impurity nuclides during the measurement process, the evaluated value is resulted in a high degree of uncertainty, which can’t meet the requirements of low fission burnup analysis. Therefore, it is of practical application value to determine the half-life of 90Rb. In this work, the half-life of 90Rb was tracked and measured by the reference source method with a better energy resolution coaxial HPGe γ spectrometer. During the measurement, characteristic γ radiations of 60Co reference source (1 173.23 keV and 1 332.50 keV) and 90Rb determine source (3 534.24, 4 135.51 and 4 365.9 keV) were tracked. In order to avoid the influence of counting correction caused by dead time and pulse pile-up during the measurement, the ratio R between the counting of 90Rb γ radiations (3 534.24, 4 135.51 and 4 365.9 keV) and the counting of the two characteristic energy (1 173.23 keV and 1 332.50 keV) of 60Co was calculated. By means of weighted linear fitting method, the slope of the ln R-t fitting curve was obtained, and the experimental values of 90Rb half-life were calculated. The uncertainty of the experimental values was comprehensively considered, taking into account the uncertainty introduced by linear fitting and statistical counting. Finally, the weighted average of the experimental values was calculated and the final half-life value with a combined uncertainty was obtained as (160.50±0.47) s (±0.29%). In order to test the reliability of the final half-life value, the relative uncertainty of the data points in each fitting curve was obtained by amplifying the difference between the data points in each fitting curve. It can be found that data points with a relative uncertainty within 1σ account for about 70% of the total data points, 2σ for about 95% and 3σ for 100%, proving the reliability of the given half-life value. The final half-life value has lower uncertainties than that of literature values and agrees with the ENSDF values (158±5) s (±3.2%). The results of this work will provide data support for rapid and accurate measurement of low fission burnup in the future.

Abstract Background The association between gastrointestinal cancer and types of meat consumption, including red meat, processed meat, or a combination of both, remains disputable. Therefore, we performed a systematic review and meta-analysis of prospective cohort studies to estimate the association between meat consumption and gastrointestinal cancer risk. Methods PubMed, EmBase, and the Cochrane library databases were searched systematically for eligible studies that investigated the relation between meat consumption and the risk of developing gastrointestinal cancers, including esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), colon cancer (CC), rectal cancer (RC), pancreatic cancer (PC), and hepatocellular carcinoma (HCC) throughout February, 2023. The pooled relative risk (RR) with 95% confidence interval (CI) was assigned as an effect estimate and calculated using a random-effects model with inverse variance weighting. Results Forty cohorts comprising 3,780,590 individuals were selected for the final quantitative analysis. The summary results indicated that a higher red meat consumption was associated with an increased risk of CRC (RR: 1.09; 95% CI: 1.02–1.16; P = 0.007) and CC (RR: 1.13; 95% CI: 1.03–1.25; P = 0.011). Moreover, a higher processed meat consumption was associated with an increased risk of CRC (RR: 1.19; 95% CI: 1.13–1.26; P

Abstract Background The advantages of parenchymal-sparing resection (PSR) over anatomic resection (AR) of colorectal liver metastases (CRLM) remain controversial. Here, we aim to evaluate their safety and efficacy. Methods A systematic review and meta-analysis of short-term perioperative outcomes and long-term oncological outcomes for PSR and AR were performed by searching Pubmed, Embase, the Cochrane Library and Web of Science databases. Results Twenty-two studies were considered eligible (totally 7228 patients: AR, n = 3154 (43.6%) vs. PSR, n = 4074 (56.4%)). Overall survival (OS, HR = 1.08, 95% CI: 0.95-1.22, P = 0.245) and disease-free survival (DFS, HR = 1.09, 95% CI: 0.94-1.28, P = 0.259) were comparable between the two groups. There were no significant differences in 3-year OS, 5-year OS, 3-year DFS, 5-year DFS, 3-year liver recurrence-free survival (liver-RFS) and 5-year liver-RFS. In terms of perioperative outcome, patients undergoing AR surgery were associated with prolonged operation time (WMD = 51.48 min, 95% CI: 29.03-73.93, P

Abstract A comorbidity of chronic pain is sleep disturbance. Here, we identify a dual-functional ensemble that regulates both pain-like behaviour induced by chronic constrictive injury or complete Freund’s adjuvant, and sleep wakefulness, in the nucleus accumbens (NAc) in mice. Specifically, a select population of NAc neurons exhibits increased activity either upon nociceptive stimulation or during wakefulness. Experimental activation of the ensemble neurons exacerbates pain-like (nociceptive) responses and reduces NREM sleep, while inactivation of these neurons produces the opposite effects. Furthermore, NAc ensemble primarily consists of D1 neurons and projects divergently to the ventral tegmental area (VTA) and preoptic area (POA). Silencing an ensemble innervating VTA neurons selectively increases nociceptive responses without affecting sleep, whereas inhibiting ensemble-innervating POA neurons decreases NREM sleep without affecting nociception. These results suggest a common NAc ensemble that encodes chronic pain and controls sleep, and achieves the modality specificity through its divergent downstream circuit targets.

Background: The tissue response viewer (TRV) is a multiparametric index that incorporates time, power, tissue pressure, impedance, and wall thickness data during radiofrequency catheter ablation (RFCA) and is used to predict the transmurality of lesions. This study aimed to evaluate the feasibility and accuracy of the TRV in a porcine model. Methods: Twelve pigs underwent preablation high-density voltage and activation mapping of two atria, and both were repeated after linear RFCA. Intentional gaps were kept in the left atrium (LA) and were touched up in the right atrium (RA). Standard and high powers were, respectively, performed in the LA ablation. Six pigs were immediately sacrificed for pathological examination after the mapping and ablation procedure (acute study). Another six pigs were kept for 4 weeks before remapping and pathological examination (chronic study). Results: All animals completed the planned procedure. The TRV function showed a sensitivity of 97.1% and a specificity of 76.9% in the acute study, and a sensitivity of 95.9% and a specificity of 72.5% in the chronic study to predict the transmural lesion. All positive and negative predictive values were over 80%. In addition, the TRV achieved higher sensitivity (92.3% vs. 85.0%) and specificity (88.2% vs. 78.9%) to predict the transmural lesion in LA ablation with high power compared with standard ablation. Conclusions: This study presents the histopathological validation of TRV to predict transmural lesions. The use of TRV may guide a more individual ablation and a more precise touch-up of gaps for atrial arrhythmias.

Iron is essential for living organisms. Iron-containing proteins play a key role in cell function, while iron overload produces reactive oxygen species through electron transfer, resulting in DNA damage, oxidative stress, metabolic disorder and tissue as well as organ dysfunction. Liver is the main organ of iron storage and is related to regulating the metabolism, utilization and excretion of iron and maintaining iron homeostasis. Iron overload is common in patients with liver diseases, which is closely related to the occurrence and development of liver diseases.

Abstract Cancer cells consistently utilize the unfolded protein response (UPR) to encounter the abnormal endoplasmic reticulum (ER) stress induced by the accumulation of misfolded proteins. Extreme activation of the UPR could also provoke maladaptive cell death. Previous reports have shown that NRF2 antioxidant signaling is activated by UPR and serves as noncanonical pathway to defense and reduce excessive ROS levels during ER stress. However, the mechanisms of regulating NRF2 signaling upon ER stress in glioblastoma have not been fully elucidated. Here we identify that SMURF1 protects against ER stress and facilitates glioblastoma cell survival by rewiring KEAP1-NRF2 pathway. We show that ER stress induces SMURF1 degradation. Knockdown of SMURF1 upregulates IRE1 and PERK signaling in the UPR pathway and prevents ER-associated protein degradation (ERAD) activity, leading to cell apoptosis. Importantly, SMURF1 overexpression activates NRF2 signaling to reduce ROS levels and alleviate UPR-mediated cell death. Mechanistically, SMURF1 interacts with and ubiquitinates KEAP1 for its degradation (NRF2 negative regulator), resulting in NRF2 nuclear import. Moreover, SMURF1 loss reduces glioblastoma cell proliferation and growth in subcutaneously implanted nude mice xenografts. Taken together, SMURF1 rewires KEAP1-NRF2 pathway to confer resistance to ER stress inducers and protect glioblastoma cell survival. ER stress and SMURF1 modulation may provide promising therapeutic targets for the treatment of glioblastoma.

Highlights 4-nm-thick Pt nanosheets (Pt-NSs) are electrochemically grown on Ti substrates for hydrogen evolution reactions. Highly uniform Pt-NS surface coverage with an ultralow loading of 0.015 mgPt cm−2 is achieved. 99.5% catalyst savings and about 237-fold higher catalyst utilization are demonstrated.

[Objective] The objective of this study was to determine how the response relationship between urban riparian land use and water quality changes due to different drainage systems and riparian buffers in order to provide a practical reference for the planning and development of urban riparian zones resulting in improved water environment and ecological restoration. [Methods] We used redundancy analysis and the ecological landscape pattern method with water quality and land use data from Suzhou Creek in Shanghai in 2018 to quantitatively determine the response of river water quality to land use change for different drainage systems and different widths of riparian buffer zones. [Results] ① Land use structure and water quality of the Suzhou Creek riparian area showed obvious spatial and temporal differences between the self-drainage area and the sewer-drainage area. Water quality during the flood season (April-October) was worse than during the non-flood season, and water quality in the self-drainage area was generally better than in the sewer-drainage area. ② Landscape patch density of the water area and agricultural land in the riparian zone of the self-drainage area significantly affected the variation of water quality in the 100—600 m buffer width. ③ Proportion and patch dominance of ecological land significantly affected the variation of water quality in the riparian zone of the sewer-drainage area, and impacted water quality in a range of 100—1 200 meters of the riparian buffer width. ④ Land use accounted for the greatest amount water quality change (56.9%) in the buffer width of the 1 200 m riparian zone in the sewer-drainage area. The explanatory ability of the sewer-drainage area (44.1%—56.9%) was generally higher than that of the self-drainage area (31.1%—52.8%). [Conclusion] There were significant spatial differences in the key variables that influenced the relationship between riparian land use and water quality in the self-drainage area and the sewer-drainage area. In addition, landscape pattern showed a more intensive influence and a larger effect on the variation of water quality in the sewer-drainage area of the riparian zone.

Key clinical message Unicentric Castleman disease, particularly the hypervascular variant subtype, commonly presents as a localized lymphadenopathy without systemic symptoms. Surgical excision is often curative for this subtype, leading to a good prognosis. However, some patients with autoimmune complications may require additional systemic therapy along with surgery. Accurate diagnosis through a combination of clinical, radiological, and pathological findings is crucial for optimal management.

Background: The vein of Marshall (VOM) ethanol infusion improves rhythm control in atrial fibrillation (AF). The identification and cannulation of the VOM can be technically challenging. This study aimed to assess the angiographic morphology of the VOM and investigate its value in the VOM ethanol infusion. Methods: Patients with AF (n = 162) scheduled for combined catheter ablation and VOM ethanol infusion were enrolled. The VOM morphologic features in the right anterior oblique (RAO), the left anterior oblique (LAO), and the LAO cranial views were analyzed. The impact of morphology on the identification and cannulation of the VOM was investigated. Results: The VOM was identified in 159 (98.1 %) and cannulated in 150 (92.6 %) patients. The VOM identification rate in the RAO and LAO/LAO cranial view was 97.3 % and 89.3 %, respectively. Of 134 patients with VOM identification in the LAO/LAO cranial view, 104 (77.6 %) had a VOM ostium clock location (VOMoClock) of ≤3 and 3–4 o'clock. The VOM cannulation success rate in the ≤3, 3–4, 4–5, and 5–6 o'clock groups was 100 %, 92.6 %, 88.5 %, and 77.8 %, respectively (p = 0.032). The median (interquartile range) cannulation time in the four groups was 10.5 (6.3), 12.0 (9.0), 13.0 (23.0), and 34.0 (30.0) minutes, respectively (p

Abstract Getting access to administrative health data for research purposes is a difficult and time-consuming process due to increasingly demanding privacy regulations. An alternative method for sharing administrative health data would be to share synthetic datasets where the records do not correspond to real individuals, but the patterns and relationships seen in the data are reproduced. This paper assesses the feasibility of generating synthetic administrative health data using a recurrent deep learning model. Our data comes from 120,000 individuals from Alberta Health’s administrative health database. We assess how similar our synthetic data is to the real data using utility assessments that assess the structure and general patterns in the data as well as by recreating a specific analysis in the real data commonly applied to this type of administrative health data. We also assess the privacy risks associated with the use of this synthetic dataset. Generic utility assessments that used Hellinger distance to quantify the difference in distributions between real and synthetic datasets for event types (0.027), attributes (mean 0.0417), Markov transition matrices (order 1 mean absolute difference: 0.0896, sd: 0.159; order 2: mean Hellinger distance 0.2195, sd: 0.2724), the Hellinger distance between the joint distributions was 0.352, and the similarity of random cohorts generated from real and synthetic data had a mean Hellinger distance of 0.3 and mean Euclidean distance of 0.064, indicating small differences between the distributions in the real data and the synthetic data. By applying a realistic analysis to both real and synthetic datasets, Cox regression hazard ratios achieved a mean confidence interval overlap of 68% for adjusted hazard ratios among 5 key outcomes of interest, indicating synthetic data produces similar analytic results to real data. The privacy assessment concluded that the attribution disclosure risk associated with this synthetic dataset was substantially less than the typical 0.09 acceptable risk threshold. Based on these metrics our results show that our synthetic data is suitably similar to the real data and could be shared for research purposes thereby alleviating concerns associated with the sharing of real data in some circumstances.

Abstract Background Colon cancer is a common and highly malignant tumor. Its incidence is increasing rapidly with poor prognosis. At present, immunotherapy is a rapidly developing treatment for colon cancer. The aim of this study was to construct a prognostic risk model based on immune genes for early diagnosis and accurate prognostic prediction of colon cancer. Methods Transcriptome data and clinical data were downloaded from the cancer Genome Atlas database. Immunity genes were obtained from ImmPort database. The differentially expressed transcription factors (TFs) were obtained from Cistrome database. Differentially expressed (DE) immune genes were identified in 473 cases of colon cancer and 41 cases of normal adjacent tissues. An immune-related prognostic model of colon cancer was established and its clinical applicability was verified. Among 318 tumor-related transcription factors, differentially expressed transcription factors were finally obtained, and a regulatory network was constructed according to the up-down regulatory relationship. Results A total of 477 DE immune genes (180 up-regulated and 297 down-regulated) were detected. We developed and validated twelve immune gene models for colon cancer, including SLC10A2, FABP4, FGF2, CCL28, IGKV1-6, IGLV6-57, ESM1, UCN, UTS2, VIP, IL1RL2, NGFR. The model was proved to be an independent prognostic variable with good prognostic ability. A total of 68 DE TFs (40 up-regulated and 23 down-regulated) were obtained. The regulation network between TF and immune genes was plotted by using TF as source node and immune genes as target node. In addition, Macrophage, Myeloid Dendritic cell and CD4+ T cell increased with the increase of risk score. Conclusion We developed and validated twelve immune gene models for colon cancer, including SLC10A2, FABP4, FGF2, CCL28, IGKV1-6, IGLV6-57, ESM1, UCN, UTS2, VIP, IL1RL2, NGFR. This model can be used as a tool variable to predict the prognosis of colon cancer.

TRIM72 oligomerization via intermolecular disulfide bonds is important for cells to repair damaged membranes. Here, authors report the crystal structure of TRIM72 dimer and show that TRIM72 B-box dimerization facilitates TRIM72 oligomerization.

Abstract Background The lateral anatomical and morphological characteristics of knees with varus knee osteoarthritis (OA) have not received sufficient attention. This study used several radiological parameters to describe the morphological characteristics of the lateral knee with OA to determine whether there are relationships between varus knee OA and parameters such as lateral plateau widening (LPW), proximal fibula curvature (PFC), and fibula height (FH). Methods The study retrospectively analyzed 1072 subjects who underwent standard radiography for diagnosing or evaluating symptomatic knee joint disease. The 163 Kellgren and Lawrence (K–L) grades 0 and I knees were categorized into the no-knee-OA group, and the 909 K–L grades II–IV knees were classified into the knee-OA group. Medial proximal tibial angle, joint line convergence angle, hip–knee–ankle angle, LPW, PFC, and FH were measured. T tests and chi-square tests were used to compare each index between the two groups. Binary logistic regression was performed to examine the correlation between indexes and knee OA occurrence. Ordinal logistic analysis, principal component analysis, and multivariable linear regression analysis were performed to examine the correlations between the three lateral parameters and K–L grades and the degree of varus deformity. Results LPW and PFC were significantly greater and FH was significantly smaller in the knee-OA group than in the no-knee-OA group. LPW, PFC, and FH were correlated with knee OA occurrence. One principal component, named the comprehensive principal component score of varus deformity, was extracted from the three indexes, and the total variance of the principal component interpretation was 76.60%. Ordinal logistics and multivariable linear regression analysis showed that, after adjusting for age and BMI, LPW and PFC were positively correlated with K–L grading and varus deformity. FH was significantly and negatively correlated with K–L grading and varus deformity (all P

Abstract Exosomes in the body fluid are effective cell-derived membranous structures transferring various molecules to mediate intercellular communication. The expression of protein in the urinary exosomes from the colorectal cancer (CRC) patients could reflect the characteristics of tumorigenesis. The urinary exosomes with globular membrane structure, the size of 30 ~ 100 nm and positive expression of CD9, CD63 and CD81 were successfully isolated from 9 CRC patients and 3 heathy adults using the density gradient ultracentrifugation. Proteome profiles revealed by label-free liquid chromatography-tandem mass spectrometry (LC–MS/MS) indicated that several proteins were differentially expressed among different stages of CRC. Compared with normal controls, 67 proteins in CRC urinary exosomes were upregulated and 74 proteins were downregulated. The bioinformatics analysis revealed the decreased proteins were related to ESCRT III complex disassembly. The CHMP family was further determined to be the hub of interaction network of proteins enriched in ESCRT signaling. The significant decrease of CHMP4A, CHMP4B, CHMP2A, CHMP2B and CHMP1B were respectively found in the total CRC group and distant metastasis group compared with NC group. Moreover, the CEACAM family also showed significant aberrant changes in the urinary exosomes of CRC patients. The CEACAM7 and CEACAM1 were increased in the CRC patients compared with healthy individuals (P

Recent studies revealed the relationship among homologous recombination repair (HRR), androgen receptor (AR), and poly(adenosine diphosphate-ribose) polymerase (PARP); however, the synergy between anti-androgen enzalutamide (ENZ) and PARP inhibitor olaparib (OLA) remains unclear. Here, we showed that the synergistic effect of ENZ and OLA significantly reduced proliferation and induced apoptosis in AR-positive prostate cancer cell lines. Next-generation sequencing followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed the significant effects of ENZ plus OLA on nonhomologous end joining (NHEJ) and apoptosis pathways. ENZ combined with OLA synergistically inhibited the NHEJ pathway by repressing DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and X-ray repair cross complementing 4 (XRCC4). Moreover, our data showed that ENZ could enhance the response of prostate cancer cells to the combination therapy by reversing the anti-apoptotic effect of OLA through the downregulation of anti-apoptotic gene insulin-like growth factor 1 receptor (IGF1R) and the upregulation of pro-apoptotic gene death-associated protein kinase 1 (DAPK1). Collectively, our results suggested that ENZ combined with OLA can promote prostate cancer cell apoptosis by multiple pathways other than inducing HRR defects, providing evidence for the combined use of ENZ and OLA in prostate cancer regardless of HRR gene mutation status.

Most prostate cancers initially respond to androgen deprivation therapy (ADT). With the long-term application of ADT, localized prostate cancer will progress to castration-resistant prostate cancer (CRPC), metastatic CRPC (mCRPC), and neuroendocrine prostate cancer (NEPC), and the transcriptional network shifted. Forkhead box protein A1 (FOXA1) may play a key role in this process through multiple mechanisms. To better understand the role of FOXA1 in prostate cancer, we review the interplay among FOXA1-targeted genes, modulators of FOXA1, and FOXA1 with a particular emphasis on androgen receptor (AR) function. Furthermore, we discuss the distinct role of FOXA1 mutations in prostate cancer and clinical significance of FOXA1. We summarize possible regulation pathways of FOXA1 in different stages of prostate cancer. We focus on links between FOXA1 and AR, which may play different roles in various types of prostate cancer. Finally, we discuss FOXA1 mutation and its clinical significance in prostate cancer. FOXA1 regulates the development of prostate cancer through various pathways, and it could be a biomarker for mCRPC and NEPC. Future efforts need to focus on mechanisms underlying mutation of FOXA1 in advanced prostate cancer. We believe that FOXA1 would be a prognostic marker and therapeutic target in prostate cancer.